Iron uptake for heme and hemoglobin synthesis in erythropoietic cells occurs by receptor-mediated endocytosis of transferrin. The purpose of these studies is to define and characterize the nature of events which are implicated in transferrin-mediated iron delivery and its regulation in rat reticulocytes and to determine how and if heme synthesis regulate the iron delivery mechanism to control iron uptake. Biochemical and functional studies of the iron delivery process seek to determine the extent to which iron uptake is dependent upon calcium influx or its mobilization from intracellular stores, the role of protein kinase C, and the significance of phosphorylation of receptor, membrane, and membrane-associated proteins in the control of iron delivery. Analysis of the mechanism of action of dansylcadaverine, a potent inhibitor of transferrin-mediated iron delivery, will be performed to determine the molecular basis of its effects on iron uptake, particularly with emphasis upon the possible role of metalloendoproteases in receptor-mediated membrane flow. The long-term objective of these studies is to determine the mutual co-ordination of hemoglobin synthesis and iron metabolism in developing red blood cells. The results of these studies may have significant implications in our understanding of human red cell disorders which are characterized by aberrant iron metabolism.